{"doi":"10.1126/sciadv.ade6675","title":"The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy","abstract":"Reactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Here, we investigated the impact of the BAF complex inhibitor pyrimethamine on the reservoir of people living with HIV-1 (PLWH). Twenty-eight PLWH on suppressive antiretroviral therapy were randomized (1:1:1:1 ratio) to receive pyrimethamine, valproic acid, both, or no intervention for 14 days. The primary end point was change in cell-associated unspliced (CA US) HIV-1 RNA at days 0 and 14. We observed a rapid, modest, and significant increase in (CA US) HIV-1 RNA in response to pyrimethamine exposure, which persisted throughout treatment and follow-up. Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine. Pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir. These data demonstrate that the licensed drug pyrimethamine can be repurposed as a BAF complex inhibitor to reverse HIV-1 latency in vivo in PLWH, substantiating its potential advancement in clinical studies.","journal":"Science Advances","year":2023,"id":357337,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9683,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1106810,"name":"Raquel Crespo","orcid":"0000-0002-6751-6621","position":1,"is_corresponding":false},{"id":948231,"name":"Cynthia Lungu","orcid":"0000-0003-1231-9628","position":2,"is_corresponding":false},{"id":271420,"name":"Shringar Rao","orcid":"0000-0003-2242-7331","position":3,"is_corresponding":false},{"id":1106811,"name":"Letao Li","orcid":"0000-0002-4692-9689","position":4,"is_corresponding":false},{"id":231806,"name":"Ronald J. Overmars","orcid":"0000-0002-8984-0633","position":5,"is_corresponding":false},{"id":1106812,"name":"Grigorios Papageorgiou","orcid":"0000-0003-2189-7120","position":6,"is_corresponding":false},{"id":1106813,"name":"Yvonne M. Mueller","orcid":"0000-0002-4654-7509","position":7,"is_corresponding":false},{"id":1106814,"name":"Mateusz Stoszko","orcid":"0000-0002-0629-2492","position":8,"is_corresponding":false},{"id":1041693,"name":"Tanvir Hossain","orcid":"0000-0002-4765-6600","position":9,"is_corresponding":false},{"id":1106815,"name":"Tsung Wai Kan","orcid":"0009-0001-0013-8486","position":10,"is_corresponding":false},{"id":804432,"name":"Bart Rijnders","orcid":"0000-0003-3343-9610","position":11,"is_corresponding":false},{"id":715468,"name":"Hannelore I. Bax","orcid":"0000-0003-0076-5479","position":12,"is_corresponding":false},{"id":107147,"name":"Eric C. M. Van Gorp","orcid":"0000-0001-6415-6678","position":13,"is_corresponding":false},{"id":1106816,"name":"Jan Nouwen","orcid":"0000-0002-0106-4490","position":14,"is_corresponding":false},{"id":1107194,"name":"T.E.M.S. de Vries-Sluijs","orcid":null,"position":15,"is_corresponding":false},{"id":948232,"name":"Carolina A. M. Schurink","orcid":"0000-0002-2766-5147","position":16,"is_corresponding":false},{"id":1106817,"name":"Mariana de Mendonça Melo","orcid":"0000-0002-7315-8226","position":17,"is_corresponding":false},{"id":1106818,"name":"Els van Nood","orcid":"0000-0002-4962-4792","position":18,"is_corresponding":false},{"id":954199,"name":"Angela Colbers","orcid":"0000-0002-0389-9934","position":19,"is_corresponding":false},{"id":468058,"name":"David M. Burger","orcid":"0000-0001-7279-2818","position":20,"is_corresponding":false},{"id":1106819,"name":"Robert‐Jan Palstra","orcid":"0000-0003-4600-2303","position":21,"is_corresponding":false},{"id":501026,"name":"Jeroen J. A. van Kampen","orcid":"0000-0002-7625-8230","position":22,"is_corresponding":false},{"id":36915,"name":"David van de Vijver","orcid":"0000-0001-5877-8526","position":23,"is_corresponding":false},{"id":388200,"name":"Thibault Mésplède","orcid":"0000-0003-0515-9128","position":24,"is_corresponding":false},{"id":28815,"name":"Peter D. Katsikis","orcid":"0000-0001-7690-5218","position":25,"is_corresponding":false},{"id":948234,"name":"Rob A. Gruters","orcid":"0000-0002-8486-5903","position":26,"is_corresponding":false},{"id":866226,"name":"Birgit C. P. 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